Mechanism of oxygen supply to tissue will be studied by using several new biochemical and biophysical techniques. Synthetic green hemoglobins with different oxygen affinities will be used as a new type of reporter molecules to investigate hemoglobin behavior at the molecular and cellular levels. A sensitive automatic oxygen equilibrium apparatus for hemoglobin and red cell suspensions, will be used in order to evaluate the efficiency of oxygen transport by hemoglobin. Since synthetic hemoglobins have different colors from those of native hemoglobin, myoglobin and other tissue hemoproteins, the oxy-deoxy transition of hemoglobin and myoglobin can be independently monitored by the difference of absorption changes. Spin-label method will also be used to study the interaction between hemoglobin subunits. The spin-labels attached directly to heme, provide important information about the conformational change of protein due to oxygen binding or due to subunit-subunit interaction. It is also possible to prepare various hybrid hemoglobins in which only one type of subunit has a different color. Accurate studies of oxygen binding to these hybrid hemoglobins will provide important information about the molecular mechanism of oxygen binding, particularly the mechanism of heme-heme interaction of hemoglobin. The new methods for studying hemoglobin function proposed in this supplement will provide complementary information to that gained from spin-labeled studies of hemoglobin. These fundamental studies of hemoglobin will provide a basis for further understanding and treatment of hemoglobinopathies and disorders of oxygen transport. BIBLIOGRAPHIC REFERENCES: Asakura, T., Segal, M. E., Friedman, S., and Schwartz, E. A Rapid Test for Sickle Hemoglobin, JAMA 233, 156 (1975). Asakura, T., Sono, M., Shapiro, M., Martinez, J., and SChwartz, E. Several New Properties of Hemoglobin Koln, Fed. Proc., 34, 687 (1975).